We will elaborate serum quantitative-PCR (QPCR) and peripheral blood RT-QPCR tests to diagnose the presence of sarcomas. We aim to construct simple blood tests to screen people at increased risk for sarcoma, to evaluate the initial tumor, to assess therapy of patients with sarcoma and/or to follow people who have been treated for sarcoma. Sarcomas were chosen initially because we found appreciable amounts of lysed tumor cell DNA in the serum. This enabled us to propose a generic test based on quantitative differences of tumor suppressors and oncogenes in sarcoma. Subsequently, more specific tests have become available involving aberration of the c-kit gene in GI stromal tumors and specific translocations that characterize defined sarcoma types. We add these more specific tests to our previous application that was based on the generic tests only. 1. Test the primary sarcoma to assay the QPCR markers that show quantitative changes and the RT-QPCR markers that show specific translocations. 2. Monitor the serum simultaneously to determine the QPCR anomalies therein and/or the peripheral blood to screen for specific RT-QPCR markers of translocation. The usefulness of these determinations is supported by our preliminary results demonstrating the presence of QPCR serum anomalies in untreated sarcoma patients. 3. Monitor the serum and peripheral blood longitudinally to screen for these molecular anomalies and (if necessary) new anomalies to detect metastases and/or recurrence that might not be apparent clinically. If we detect useful serum QPCR anomalies and/or peripheral blood anomalies in particular situations in phase I, we will expand the studies in phase II to perform longitudinal QPCR assays useful in a given situation. We will use the test to perform diagnosis of at-risk and treated populations, to monitor cancer cell lysis before and during treatment, to monitor the efficacy of cancer treatments and to detect recurrences. This is proposed as an R21 (one year)/R33 (three year) grant to determine the feasibility of these studies for sarcomas in the R21 phase. If more studies are indicated, the R33 phase would support the longer-term longitudinal studies required to demonstrate how best to use this test to follow the course of sarcomas.